Prader-Willi (Dr. Elias - L2) Flashcards Preview

Ann's M2M - Weeks 3, 4 > Prader-Willi (Dr. Elias - L2) > Flashcards

Flashcards in Prader-Willi (Dr. Elias - L2) Deck (17)
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0
Q

In a child with PW what is likely to be seen on a FISH test?

Why might this finding not always occur in a PW diagnosis?

A

likely: del(15)(q11-q13) deletion on long arm of paternal chrom. 15

also possible: uniparental disomy; two copies of chrom 15 from mom, none from dad

1
Q

What is a common finding, during pregnancy, if a fetus has PW?
What is notable immediately at birth?

A

decreased fetal movements

hypotonic (floppy)
dysmorphic (unusual facial features)
almond shaped eyes
cryptorchidism (undescended testicles)

2
Q

Due to the hypotonia seen in PW infants, what are some common complications?

A

Feeding issues

may need a gastrostomy tube

3
Q

What is strabismus and nystagmus?

A
strabismus = lazy eye
nystagmus = jiggly eye
4
Q

What is the hallmark symptom that develops in a child with PW around pre-school age?

A

Hyperphagia

–> weight gain

5
Q

What is a common early treatment for PW and what symptom is a contraindication for this treatment?

A

Growth Hormone

contraindicated if the child has obstructive sleep apnea.

6
Q

Do patients with PW have intellectual disabilities?

A

Yes, mild to moderate.

7
Q

Explain briefly how a FISH would pick up a deletion on chromosome 15 indicating PW

A

A chromosome 15 probe labels the chromosome 15.
A SNRPN probe is added and if it does not attach to one of the chr. 15’s that indicates a deletion of the region associated with PW.

5’UTR of the SNRPN gene is an imprinting center and will be methylated (silenced) in uniparental disomy cases of PW.

8
Q

What other disorder can be caused by a deletion on the long arm of chromosome 15?

A

Angleman’s syndrome. deletion on the maternal allele.

del(15)(q11-q13)

9
Q

How could you distinguish whether PW syndrome is caused by a deletion on the parental chrm 15 or UPD?

A

UPD would be indicated by two chromosome 15’s both with the maternal imprinting (methylation) pattern.

This can be from a methylation (imprinting) error on the father’s chr. 15 or it can be from two maternal chr. 15’s and no paternal chr. 15

10
Q

List some common medical issues seen in PW patients.

A

Eyes: strabismus, nystagmus
Ortho: scoliosis
Respiratory: obstructive sleep apnea (which contraindicates use of GH to treat)
Developmentally: mild-moderate cognitive disabilities; behavioral issues; picking & scratching disorders = skin issues

11
Q

What neurotransmitter on the b3 locus of chrom. 15 is thought to be affected in pts with Autism?

A

GABA
gamma-aminobutyric acid

encoding for certain GABA receptors located in the 15q11-13 region affected in maternal deletions

12
Q

idic15?

A

Inverted, duplicated isodicentric 15q

phenotype is hypotonia, severe intellectual disabilities, autism and seizures

13
Q

Discuss the genetic mechanisms leading to Angelman’s syndrome

A
  1. deletion in 15q11-13 (PWSAS region) on maternal allele
  2. UBE 3A mutation on maternal allele
  3. Paternal UPD (missing mother’s copy completely)
  4. Imprinting defect (maternal allele is imprinted with paternal pattern; “looks” like paternal UPD)
14
Q

Gene associated with Prader-Willi syndrome?

A

On chromosome 15, gene is SNORD116

15
Q

Gene associated with Angleman’s syndrome?

A

UBE3A on chromosome 15

16
Q

Consider the case of uniparental disomy cause of either Angelmans syndrome or Prader-Willi syndrome.

If the disomy is an isodisomy, when did the nondisjunction occur?
If the disomy is heterodisomy, when did the nondisjunction occur?

A

PW: isodisomy = maternal meiosis II
heterodisomy = maternal meiosis I

AS: isodisomy = paternal meiosis II
heterodisomy = paternal meiosis I